The present invention provides methods for the calibration of detection and/or quantification assays of a wide range of analytes.
All in vitro diagnostic assays require calibration in order to accurately determine the analyte level of samples or specimens. This has usually been accomplished by generating a standard curve from the measurement of samples of known value. Specimens with unknown levels of analyte can then be measured and compared to the standard curve using mathematically derived relationships. The standard curve may be determined prior to or concurrently with analysis of the sample specimens, depending on the stability and reproducibility of the assay. Methods producing results that vary considerably from assay to assay require that standardization be determined concurrently with each assay. This is undesirable as it increases both cost and time. Assay methods that allow the use of previously determined standards, such as a stored standard curve, and that do not require standardization with each assay would be preferable.
In cases where assay results vary considerably from one assay to the next or over time, the simultaneous measurement of a standard sample of known value with the unknown sample may allow adjustment of standard curves and calculation of accurate results. This method, however, requires that the concurrently run standard be stable over the shelf life of the assay and be measured in the assay method identically to the unknown sample. In dried assay method systems this requirement may be extremely difficult to achieve. It would therefore be desirable to be able to deliver an unmeasured and variable amount of calibrator into a dried reagent assay system and be able to use the results, in association with a previously determined standardization algorithm, to accurately predict unknown analyte levels, regardless of assay perturbations.
The present invention is applicable to a wide variety of both wet and dry chemistry assay systems. A particular type of dry chemistry assay system in which the present invention is useful is described in PCT Publication WO 00/58730, published Oct. 5, 2000.